Accessing chemical diversity from the uncultivated symbionts of small marine animals.

Accessing chemical diversity from the uncultivated symbionts of small marine animals.
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从小型海洋动物未经培养的共生体中获取化学多样性。

DOI:
10.1038/nchembio.2537
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发表时间:
2018-03
影响因子:
14.8
通讯作者:
Schmidt EW
Schmidt EW
中科院分区:
生物学1区
文献类型:
--
作者:
Smith TE;Pond CD;Pierce E;Harmer ZP;Kwan J;Zachariah MM;Harper MK;Wyche TP;Matainaho TK;Bugni TS;Barrows LR;Ireland CM;Schmidt EW

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化学驱动了微生物群和宿主动物之间的许多生物相互作用,但识别所涉及的化学物质通常具有挑战性。这就带来了一个问题,因为这些小分子是潜在药物的极好来源,并且经过了大自然的动物相容性预先测试。我们从巴布亚新几内亚东部地区的小型海洋被囊动物中发现了抗艾滋病毒化合物。被囊类动物是新型生物活性化学物质的储存库,但它们的体积较小,常常妨碍识别甚至检测其中的化学物质。我们通过结合化学、宏基因组学和合成生物学来直接识别和合成天然产物来解决这个问题。我们证明这些抗 HIV 化合物,二酰胺,是由生活在被囊动物中的共生细菌产生的新型羊毛肽家族。邻近的动物群体含有结构相关的二酰胺,其生物学特性截然不同,这表明生物合成可塑性在发生生物相互作用的天然环境中发挥着作用。
Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV compounds from small, marine tunicates from the Eastern Fields of Papua New Guinea. Tunicates are a reservoir for novel bioactive chemicals, yet their small size often impedes identification or even detection of the chemicals within. We solved this problem by combining chemistry, metagenomics, and synthetic biology to directly identify and synthesize the natural products. We show that these anti-HIV compounds, the divamides, are a novel family of lanthipeptides produced by symbiotic bacteria living in the tunicate. Neighboring animal colonies contain structurally related divamides that differ starkly in their biological properties, suggesting a role for biosynthetic plasticity in a native context where biological interactions take place.
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